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Stem Cell Research & Therapeutics

Review Article Volume 11 Issue 1

Next-generation cortical organoid models: from self-organization to integrated systems

Marta Montero-Crespo, Milagros Pereira Luppi, Paola Arlotta

Received: December 24, 2025 | Published: January 21, 2026

Citation: Montero-Crespo M, Luppi MP, Arlotta P. Next-generation cortical organoid models: from self-organization to integrated systems. J Stem Cell Res Ther. 2026;11(1):4-15. DOI: 10.15406/jsrt.2026.11.00214

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Abstract

Understanding human brain development remains challenging because animal models do not recapitulate many human-specific features, and access to developing human tissue is rare. Over the past decade, stem cell–derived 3D brain organoids have transformed this landscape by enabling controlled modeling of fate specification, cell diversification, migration, and emerging connectivity. Advances in patterning and culture now yield regionspecific cortical organoids that recapitulate key human cortical cell types, trajectories, and disease-relevant phenotypes. Yet current models still struggle to capture the cortex’s intricate architecture, long-range interactions, and extended maturation. In this review, we highlight emerging strategies to enhance cortical organoid complexity and the physiological relevance of their neural circuits.

Keywords: human brain development, cortical organoids, 3D brain organoids, stem cell

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©2026 Montero-Crespo, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.